Download Lasix Oral Solution (furosemide)

PRODUCT MONOGRAPH
Pr
LASIX® ORAL SOLUTION
furosemide oral solution Mfr. Std.
Oral solution 10 mg/mL
Diuretic
ATC Code: C03CA01
sanofi-aventis Canada Inc.
2905 Place Louis-R.-Renaud
Laval, Quebec H7V 0A3
Submission Control No: 196514
Lasix Oral Solution Product Monograph
Date of Revision:
September 20, 2016
s-a Version 10.0 dated September 20, 2016
Page 1 of 28
Table of Contents
PART I: HEALTH PROFESSIONAL INFORMATION ......................................................... 3
SUMMARY PRODUCT INFORMATION................................................................................ 3
INDICATIONS AND CLINICAL USE ..................................................................................... 3
CONTRAINDICATIONS .......................................................................................................... 4
WARNINGS AND PRECAUTIONS ......................................................................................... 4
ADVERSE REACTIONS........................................................................................................... 9
DRUG INTERACTIONS ......................................................................................................... 11
DOSAGE AND ADMINISTRATION ..................................................................................... 15
OVERDOSAGE ....................................................................................................................... 16
ACTION AND CLINICAL PHARMACOLOGY ................................................................... 17
STORAGE AND STABILITY ................................................................................................. 18
DOSAGE FORMS, COMPOSITION AND PACKAGING .................................................... 19
PART II: SCIENTIFIC INFORMATION ............................................................................... 20
PHARMACEUTICAL INFORMATION ................................................................................. 20
CLINICAL TRIALS ................................................................................................................. 20
DETAILED PHARMACOLOGY ............................................................................................ 20
TOXICOLOGY ........................................................................................................................ 21
REFERENCES ......................................................................................................................... 23
PART III: CONSUMER INFORMATION.............................................................................. 24
Lasix Oral Solution Product Monograph
Page 2 of 28
Pr
LASIX® ORAL SOLUTION
(furosemide)
PART I: HEALTH PROFESSIONAL INFORMATION
SUMMARY PRODUCT INFORMATION
Route of
Administration
Oral
Dosage Form /
Strength
Solution 10 mg/mL
Non-medicinal Ingredients
Alcohol, butylated hydroxyanisol, butylated
hydroxytoluene, glycerine, methylparaben, natural
orange flavour, polysorbate 80, potassium sorbate,
purified water, sodium hydroxide and sorbitol.
INDICATIONS AND CLINICAL USE
LASIX® (furosemide) is indicated for:
•
•
The treatment of edema associated with congestive heart failure, cirrhosis of the liver and
renal disease including, nephrotic syndrome, as well as other edematous states amenable to
diuretic therapy.
Can also be used alone, in the control of mild to moderate hypertension, or in combination
with other antihypertensive agents in more severe cases.
Hypertensive patients who cannot be adequately controlled with thiazides will probably also not
be adequately controllable with LASIX alone.
Pediatrics
When administered to children, LASIX therapy should be instituted in the hospital, in carefully
selected patients, under close observation with frequent monitoring of serum electrolytes (see
DOSAGE AND ADMINISTRATION section).
The available pediatric data does not allow for a recommendation of a specific age range in this
population.
Geriatrics (> 61 years of age)
Use in the geriatric population is associated with differences in safety (see WARNINGS AND
PRECAUTIONS).
Lasix Oral Solution Product Monograph
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CONTRAINDICATIONS
LASIX (furosemide) is contraindicated in:
•
Patients who are hypersensitive to furosemide, sulfonamide-derived drugs or to any
ingredient in the formulation or component of the container. For a complete listing, see
the Dosage Forms, Composition and Packaging section of the product monograph.
Patients allergic to sulfonamides (e.g. sulfonamide antibiotics or sulfonylureas) may
show cross-sensitivity to furosemide.
•
Patients with complete renal shutdown. If increasing azotemia and oliguria occur during
treatment of severe progressive renal disease, the drug should be discontinued.
•
Patients with hepatic coma and precoma or in states of electrolyte depletion until the
basic condition is improved or corrected. Therapy with LASIX should not be initiated in
these patients (see WARNINGS AND PRECAUTIONS, Hepatic/Biliary/Pancreatic
section).
•
Severe hyponatremia, hypokalemia, hypovolemia, dehydration or hypotension must be
regarded as contraindications until serum electrolytes and fluid balance and blood
pressure have been restored to normal levels (see WARNINGS AND PRECAUTIONS
and ADVERSE REACTIONS sections).
•
As furosemide may be capable of displacing bilirubin from albumin at least "in vitro", it
should not be administered to jaundiced newborn infants or to infants suffering from
diseases (e.g. Rh incompatibility, familial non-hemolytic jaundice, etc.) with the potential
of causing hyperbilirubinemia and possibly kernicterus.
•
Women must not breast-feed if they are treated with furosemide (see WARNINGS AND
PRECAUTIONS section).
WARNINGS AND PRECAUTIONS
General
LASIX (FUROSEMIDE) IS A POTENT DIURETIC WHICH IF GIVEN IN EXCESSIVE
AMOUNTS CAN LEAD TO A PROFOUND DIURESIS WITH WATER AND
ELECTROLYTE DEPLETION. THEREFORE, CAREFUL MEDICAL SUPERVISION IS
REQUIRED, AND DOSE AND DOSE SCHEDULE HAVE TO BE ADJUSTED TO THE
INDIVIDUAL PATIENT'S NEEDS (SEE DOSAGE AND ADMINISTRATION).
All patients receiving LASIX therapy should be observed for signs and symptoms of fluid or
electrolyte imbalance, hyponatremia, hypochloremic alkalosis, hypovolemia, hypomagnesemia,
or hypocalcemia: dryness of the mouth, thirst, weakness, lethargy, drowsiness, restlessness,
muscle pain or cramps, muscular fatigue, hypotension, oligourea, tachycardia, arrhythmia, or
gastro-intestinal disturbances such as nausea and vomiting, increases in blood glucose and
alteration in glucose tolerance tests.
During long-term therapy a high-potassium diet is recommended. Potassium supplements may be
required especially when high doses are used for prolonged periods. Some electrolyte
Lasix Oral Solution Product Monograph
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disturbances (e.g. hypokalemia, hypomagnesemia) may increase the toxicity of certain other
drugs (e.g. digitalis preparations and drugs inducing QT interval prolongation syndrome.
Particular caution with potassium levels is necessary when the patient is on digitalis glycosides,
potassium-depleting steroids, or in the case of infants and children. Potassium supplementation,
diminution in dose, or discontinuation of LASIX therapy may be required.
Since rigid sodium restriction is conducive to both hyponatremia and hypokalemia, strict
restriction in sodium intake is not advisable in patients receiving LASIX therapy.
Urinary outflow must be secured. Patients with urinary outflow require careful monitoringespecially during the initial stages of treatment (see ADVERSE REACTIONS-Post-Market
Adverse Drug Reactions-Renal and urinary disorders section).
The possibility exists of exacerbation or activation of systemic lupus erythematosus.
Concomitant use with risperidone
In risperidone placebo-controlled trials in elderly patients with dementia, a higher incidence of
mortality was observed in patients treated with furosemide plus risperidone (7.3%; mean age
89 years, range 75-97 years) when compared to patients treated with risperidone alone (3.1%;
mean age 84 years, range 70-96 years) or furosemide alone (4.1%; mean age 80 years, range 6790 years). Concomitant use of risperidone with other diuretics (mainly thiazide diuretics used in
low dose) was not associated with similar findings.
No pathophysiological mechanism has been identified to explain this finding, and no consistent
pattern for cause of death observed. Nevertheless, caution should be exercised and the risks and
benefits of this combination or co-treatment with other potent diuretics should be considered
prior to the decision to use. There was no increased incidence of mortality among patients taking
other diuretics as concomitant treatment with risperidone. Irrespective of treatment, dehydration
was an overall risk factor for mortality (see CONTRAINDICATIONS section) and should
therefore be avoided in elderly patients with dementia.
Carcinogenesis and Mutagenesis
Carcinogenicity: Furosemide in the approximate amount of 200 mg/kg body weight daily was
administered to female mice and rats over a 2-year period with their diet. An increased incidence
of mammary adenocarcinoma was noted in the mice, but not in the rats. These tumors occurred
with a positive trend, and the incidence in the high dose group was increased compared to the
control, in addition, the high-dose rate was about five fold over the historical rate. These tumors
are considered to be associated with furosemide administration. This dose is considerably greater
than the therapeutic dose administered in human patients.
In a carcinogenicity study, rats were administered furosemide in daily doses of 15 and 30 mg/kg
body weight. Male rats in the 15 mg/kg-dose category, but not in the 30 mg/kg-dose category,
showed a marginal increase in uncommon tumours.
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Mutagenicity: In in-vitro tests on bacteria and mammalian cells, both positive and negative
results have been obtained. Induction of gene and chromosome mutations, however, has been
observed only where furosemide reached cytotoxic concentrations.
Ear/Nose/Throat
Cases of tinnitus and reversible deafness have been reported. There have also been some reports
of cases, the majority in children undergoing renal transplantation, in which permanent deafness
has occurred. In these latter cases, the onset of deafness was usually insidious and gradually
progressive up to 6 months after furosemide therapy. Hearing impairment is more likely to occur
in patients with hypoproteinemia or severely reduced renal function or in patients who are also
receiving drugs known to be ototoxic. Since this may lead to irreversible damage, these drugs
must only be used with furosemide if there are compelling medical reasons.
Endocrine and Metabolism
Increases in blood glucose and alterations in glucose tolerance tests with abnormalities of the
fasting and two-hour postprandial blood sugar levels have been observed. Rare cases of
precipitation of diabetes mellitus have been reported.
Asymptomatic hyperuricemia can occur and a gout attack may rarely be precipitated.
Hepatic/Biliary/Pancreatic
It may be advisable to hospitalize patients with hepatic cirrhosis and ascites prior to initiating
therapy. Sudden alterations of fluid and electrolyte balance in patients with cirrhosis may
precipitate hepatic coma, therefore, strict observation is necessary during the period of diuresis.
Supplemental potassium chloride and, if required, an aldosterone antagonist, are helpful in
preventing hypokalemia and metabolic alkalosis (see CONTRAINDICATIONS section).
Particularly careful monitoring is necessary in patients with hepatorenal syndrome.
Peri-Operative Considerations
Sulfonamide diuretics have been reported to decrease arterial responsiveness to pressor amines
and to enhance the effect of tubocurarine. Great caution should be exercised in administering
curare or its derivatives to patients undergoing therapy with LASIX and it is advisable to
discontinue LASIX for one week prior to any elective surgery.
Special Populations
Pregnant Women
The teratogenic and embryotoxic potential of furosemide in humans is unknown. The drug
should not be used in pregnant women or in women of childbearing potential unless in the
opinion of the attending physician the benefits to the patient outweigh the possible risk to the
foetus.
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Reproductive and teratological studies have been performed in mice, rats, rabbits, cats, dogs and
monkeys. With the exception of mice and rabbits, no abnormalities attributed to furosemide were
detected. Furosemide caused unexplained maternal deaths and abortions in the rabbit at a daily
dose of 50 mg/kg (approximately three times the maximum recommended human daily dose of
1000 mg orally) when administered between days 12 to 17 of gestation. In another study in
rabbits, a dose of 25 mg/kg caused maternal deaths and abortions. In a third study, none of the
pregnant rabbits survived a dose of 100 mg/kg. Data from the above studies indicate foetal
lethality which can precede maternal deaths.
The results of a mouse study and one of the three rabbit studies also showed an increased
incidence of distention of the renal pelvis and, in some cases, of the ureters in foetuses derived
from treated dams as compared to the incidence of foetuses from the control group.
Treatment during pregnancy requires monitoring of fetal growth.
Nursing Women
It should be noted that diuretics may partially inhibit lactation and that LASIX passes into the
breast milk. Women must not breast-feed if they are treated with furosemide (see
CONTRAINDICATIONS section).
Pediatrics
LASIX may lower serum calcium levels, and rare cases of tetany have been reported.
Accordingly, periodic serum calcium levels should be obtained.
In premature infants LASIX may precipitate nephrocalcinosis/nephrolithiasis. When
administered to premature infants with respiratory distress syndrome in the first few weeks of
life, diuretic treatment with LASIX may accentuate the risk of a patent ductus arteriosus (see
WARNINGS AND PRECAUTIONS- Monitoring and Laboratory Tests section).
Caution is required in neonates because of prolonged half-life of furosemide.
Geriatrics (> 61 years of age)
Excessive diuresis induced by LASIX may result in dehydration and reduction of blood volume,
with circulatory collapse and with the possibility of vascular thrombosis and embolism
particularly in elderly patients. LASIX may cause electrolyte depletion.
Furosemide binding to albumin may be reduced in elderly patients.
The drug is known to be substantially excreted unchanged by the kidney, and the risk of toxic
reactions to this drug may be greater in patients with impaired renal function. Because elderly
patients are more likely to have decreased renal functions, care should be taken in dose selection
and may be useful to monitor renal function.
In general dose selection for the elderly patients should be cautious, usually starting at the low
end of dosage range, reflecting the greater frequency of decreased hepatic, renal or cardiac
function, and the concomitant disease or other drug therapy.
Lasix Oral Solution Product Monograph
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Monitoring and Laboratory Tests
Frequent serum electrolyte, creatinine and CO2 content determinations should be performed
during the first few months of therapy and periodically thereafter. It is essential to replace
electrolyte losses and to maintain fluid balance so as to avoid any risk of electrolyte depletion
(hyponatremia, hypochloremia, hypokalemia, hypomagnesemia or hypocalcemia), hypovolemia,
or hypotension.
Checks on urine and blood glucose should be made at regular intervals especially in diabetics
and in those suspected of latent diabetes when receiving LASIX. Increases in blood glucose and
alterations in glucose tolerance tests with abnormalities of the fasting and two-hour postprandial
blood sugar levels have been observed.
Frequent BUN determinations during the first few months of therapy and periodically thereafter,
as well as regular observations for possible occurence of blood dyscrasias, liver damage or
idiosyncratic reactions are advisable.
Particularly careful monitoring is necessary in:
- patients with hypoproteinemia. Cautious dose titration is required.
- premature infants. Renal function must be monitored and renal ultrasonography performed.
- patients with hypotension
- patients who would be at particular risk from a pronounced fall in blood pressure (e.g.
patients with significant stenoses of the coronary arteries or of the blood vessels supplying
the brain).
- patients with hepatorenal syndrome.
- patients with latent and manifest diabetes mellitus
- patients with gout
Occupational Hazards
LASIX may lower the state of patient alertness and/or reactivity particularly at the start of
treatment as a result of a reduction in blood pressure and of other adverse reactions (see
ADVERSE REACTIONS section).
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ADVERSE REACTIONS
Clinical Trial Adverse Drug Reactions
No data available.
Post-Market Adverse Drug Reactions
Adverse reactions are categorized below by body system.
Blood and lymphatic system disorders
Anemia, eosinophilia, leukopenia and thrombocytopenia (with purpura) have occurred, as well as
agranulocytosis, aplastic anemia and hemolytic anemia.
Ear and Labyrinth disorders
Cases of tinnitus and sometimes irreversible deafness have been reported. There have also been
some reports of cases, the majority in children undergoing renal transplantation, in which
permanent deafness has occurred. In these latter cases, the onset of deafness is usually insidious
and gradually progressive up to 6 months after furosemide therapy. Hearing disorder is more
likely to occur in patients with hypoproteinemia or severely reduced renal function who are also
receiving drugs known to be ototoxic.
Vertigo has been reported.
Eye disorders
Xanthopsia and blurred vision have been reported.
Gastrointestinal disorders
Acute pancreatitis, oral and gastric burning, diarrhea, nausea, vomiting and constipation have
been reported. Rare occurence of sweet taste has been reported.
Hepatobiliary disorders
Jaundice (intrahepatic cholestatic jaundice) and cholestasis have been reported.
Immune system disorders
Hypersensitivity reactions to furosemide also include photosensitivity, paresthesia and fever.
Systemic hypersensitivity reactions include vasculitis and necrotizing angiitis.
Severe anaphylactic or anaphylactoid reactions (e.g. with shock) occur rarely.
Exacerbation or activation of systemic lupus erythematosus.
Investigations
Increase in liver transaminases has been reported.
Transient elevations of BUN have been observed, especially in patients with renal insufficiency.
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As with other diuretics, there may be an increase in serum creatinine, uric acid (this may lead to
gout attack in predisposed patients), blood urea, cholesterol and triglyceride levels during
furosemide treatment.
Metabolism and nutrition disorders
Electrolyte depletion has occurred during therapy with LASIX, especially in patients receiving
higher doses with a restricted salt intake. Electrolyte depletion (hyponatremia, hypochloremia,
hypokalemia, hypocalcemia and hypomagnesemia) manifests itself by adverse reactions
attributed to various body systems: weakness, dizziness, drowsiness, polyuria, polydipsia,
orthostatic hypotension, lethargy, sweating, bladder spasms, anorexia, vomiting, mental
confusion, meteorism, thirst, headache, muscle cramp, muscle weakness, tetany and disorder of
cardiac rhythm (see WARNINGS AND PRECAUTIONS section).
The development of electrolyte disturbances (including symptomatic) is influenced by factors
such as underlying diseases (e.g. liver cirrhosis, cardiac failure), concomitant medication and
nutrition.
Cases of Pseudo-Bartter syndrome (hypochloremia, hypokalemia, alkalosis, normal to low blood
pressures, and elevated plasma renin and aldosterone) have been reported in the context of
misuse and/or long-term use of furosemide.
Treatment with LASIX has occasionally caused some deterioration of metabolic control in cases
of manifest diabetes, or has made latent diabetes manifest.
Metabolic alkalosis may develop in the form of a gradually increasing electrolyte deficit or, e.g.
where higher furosemide doses are administered to patients with normal renal function, acute
severe electrolyte losses.
Pre-existing metabolic alkalosis (e.g. in decompensated cirrhosis of the liver) may be aggravated.
In extreme cases, hypovolemia may lead to dehydration, circulatory collapse, hemoconcentration
and thrombophilia. Thrombophlebitis and emboli have been reported.
Musculoskeletal and connective tissue disorders:
Cases of rhabdomyolysis have been reported, often in the context of severe hypokalemia.
Nervous system disorders
At the commencement of treatment, excessive diuresis may give rise, especially in elderly
patients, to a feeling of pressure in the head, dizziness, headache fainting or loss of
consciousness.
Paresthesia has been reported.
Hepatic encephalopathy in patients with hepatocellular insufficiency has been reported.
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Renal and urinary disorders
Symptoms of obstructed micturition (e.g. in hydronephrosis, prostatic hypertrophy,
ureterostenosis) may become manifest or may be aggravated during medication with diuretics.
Interstitial nephritis has been reported.
Increased production of urine may provoke or aggravate complaints in patients with an
obstruction of urinary outflow. Thus, acute retention of urine with possible secondary
complications may occur. Increases in urine sodium and chloride have also been reported.
There have been some reported cases of renal failure.
In premature infants LASIX may precipitate nephrocalcinosis/nephrolithiasis.
Skin and subcutaneous tissue disorders
Various forms of dermatitis (e.g. dermatitis bullous), including urticaria, erythema multiforme,
pemphigoid, Stevens-Johnson syndrome, toxic epidermal necrolysis, exfoliative dermatitis,
pruritus, epidermolysis bullosa, AGEP (acute generalized exanthematous pustolosis) and DRESS
(Drug Rash with Eosinophilia and Systemic Symptoms) have occurred.
Dermatologic reactions to furosemide also include purpura and rash.
Vascular disorders
Too vigorous diuresis may induce orthostatic hypotension or acute hypotensive episodes, which
may cause signs and symptoms such as impairment of concentration and reactions,
lightheadedness or orthostatic intolerance. There have been some reported cases of thrombosis.
When administered to premature infants with respiratory distress syndrome in the first few
weeks of life, diuretic treatment with LASIX may accentuate the risk of a patent ductus
arteriosus.
DRUG INTERACTIONS
Overview
Sulfonamide diuretics have been reported to decrease arterial responsiveness to pressor amines
and to enhance the effect of tubocurarine or curare-type muscle relaxants (see WARNINGS
AND PRECAUTIONS – Peri-Operative Considerations section).
In case of concomitant abuse of laxatives, the risk of an increased potassium loss should be
considered.
Glucocorticoids, carbenoxolone and licorice may also increase potassium loss.
Administration of LASIX to diabetic patients may result in possible decrease of diabetic control.
Dosage adjustments of the anti-diabetic agent may be needed.
Lasix Oral Solution Product Monograph
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Hearing impairment is more likely to occur in patients who are also receiving drugs known to be
ototoxic (e.g. aminoglycosides antibiotics, ethacrynic acid and cisplatin) (see WARNINGS AND
PRECAUTIONS section).
In edematous hypertensive patients being treated with antihypertensive agents, care should be
taken to reduce the dose of these drugs when LASIX is administered, since LASIX potentiates
their hypotensive effect.
Non-steroidal anti-inflammatory drugs (e.g. indomethacin, acetyl-salicylic acid) may attenuate
the effect of LASIX and may cause renal failure in case of pre-existing hypovolemia.
Drug-Drug Interactions
The drug interactions discussed in this section are based on either drug interaction case reports,
or studies, or potential interactions due to the expected magnitude and seriousness of the
interaction (i.e., those identified as contraindicated).
Established or Predicted Drug-Drug Interactions
Proper Name
Ref
Effect
Clinical Comments
Anticonvulsants
Carbamazepine
Phenobarbital
Phenytoin
T
↓ furosemide
diuretic effect
Anticonvulsant drugs (phenytoin, carbamazepine,
phenobarbital), which, like furosemide, undergo significant
renal tubular secretion, may also attenuate the effect of
furosemide.
T
↓ antidiabetic
drug effect
The effects of antidiabetic drugs may be reduced.
Antidiabetics
Antidiabetics
Antihypertensive Agents
ACE inhibitors
CT
↓ blood pressure
and renal
function
Angiotensin II
receptor antagonists
CT
↓ blood pressure
and renal
function
T
↓ renal function
Especially in combination with ACE inhibitors, a marked
hypotension may be seen sometimes progressing to shock. The
concomitant administration of LASIX with ACE-inhibitors may
lead to deterioration in renal function and, in isolated cases, to
acute renal failure. Consideration must be given to interrupting
the administration of furosemide temporarily or at least reducing
the dose of furosemide for three days before starting treatment
with, or increasing the dose of, an ACE inhibitor.
Especially in combination with angiotensin II receptor
antagonists, a marked hypotension may be seen sometimes
progressing to shock. The concomitant administration of LASIX
with angiotensin II receptor antagonists may lead to
deterioration in renal function and, in isolated cases, to acute
renal failure. Consideration must be given to interrupting the
administration of furosemide temporarily or at least reducing the
dose of furosemide for three days before starting treatment with,
or increasing the dose of, an angiotensin II receptor antagonist.
Cephalosporins
Cephalosporins
Lasix Oral Solution Product Monograph
Impairment of renal function may develop in patients receiving
concurrent treatment with furosemide and high doses of certain
cephalosporins.
Page 12 of 28
Proper Name
Ref
Effect
Clinical Comments
Chloral Hydrate
Chloral Hydrate
C
—
In isolated cases intravenous administration of furosemide
within 24 hours of taking chloral hydrate may lead to flushing,
sweating attacks, restlessness, nausea, increase in blood pressure
and tachycardia. Use of furosemide concomitantly with chloral
hydrate is therefore not recommended.
T
—
The concurrent use of LASIX with chlorothiazide has been
reported to decrease hypercalciuria and to dissolve some calculi.
↑ nephrotoxicity
↑ ototoxicity
Nephrotoxicity of cisplatin may be enhanced if furosemide is
not given in low doses and with positive fluid balance when
used to achieve forced diuresis during cisplatin treatment. There
is also a risk of ototoxic effects if cisplatin and furosemide are
given concomitantly.
—
Concomitant use of cyclosporine A and furosemide is associated
with increased risk of gouty arthritis secondary to furosemideinduced hyperurecemia and cyclosporine impairment of renal
urate excretion.
Chlorothiazides
Chlorothiazides
Cisplatin
Cisplatin
T
Cyclosporine
Cyclosporine
CT
Digitalis Glycosides
Digitalis Glycosides
T
↓ potassium
plasma
concentration
Some electrolyte disturbances (e.g. hypokalemia,
hypomagnesemia) may increase the toxicity of certain other
drugs (e.g. digitalis preparations and drugs inducing QT interval
prolongation syndrome). Particular caution with potassium
levels is necessary when the patient is on digitalis glycosides.
Potassium supplementation, diminution in dose, or
discontinuation of LASIX therapy may be required (see
WARNINGS AND PRECAUTIONS).
Levothyroxine
Levothyroxine
↑ then ↓ thyroid
hormones
High doses of furosemide may inhibit binding of thyroid
hormones to carrier proteins and thereby lead to an initial
transient increase in free thyroid hormones, followed by an
overall decrease in total thyroid hormone levels. Thyroid
hormone levels should be monitored.
T
↑ lithium plasma
concentration
Renal clearance of lithium is decreased in patients receiving
LASIX, resulting in increased risk of cardiotoxic and neurotoxic
effects of lithium. Therefore, it is recommended that lithium
levels be carefully monitored in patients receiving this
combination.
T
↓ furosemide
diuretic effect
Methotrexate, which like furosemide, undergoes significant
renal tubular secretion, may also attenuate the effect of
furosemide.
C
Lithium
Lithium
Methotrexate
Methotrexate
Nephrotoxic Drugs
The harmful effects of nephrotoxic drugs on the kidney may be
increased.
Non-Steroidal Anti-Inflammatory Drugs (NSAIDs)
Clinical studies have shown that the administration of
↓ furosemide
Indomethacin
CT
indomethacin can reduce the natriuretic and anti-hypertensive
diuretic effect
effect of LASIX in some patients. This response has been
Nephrotoxic Drugs
T
↑ nephrotoxicity
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Proper Name
Ref
Effect
Clinical Comments
attributed to inhibition of prostaglandin synthesis by
indomethacin. Therefore, when indomethacin is added to the
treatment of a patient receiving LASIX, or LASIX is added to
the treatment of a patient receiving indomethacin, the patient
should be closely observed to determine if the desired effect of
LASIX is obtained. Indomethacin blocks the LASIX-induced
increase in plasma-renin activity. This fact should be kept in
mind when evaluating plasma-renin activity in hypertensive
patients.
Potassium-depleting Steroids
Potassium-depleting
Steroids
T
Probenecid
Probenecid
↓ potassium
plasma
concentration
Some electrolyte disturbances (e.g. hypokalemia,
hypomagnesemia) may increase the toxicity of certain other
drugs (e.g. digitalis preparations and drugs inducing QT interval
prolongation syndrome). Particular caution with potassium
levels is necessary when the patient is on potassium-depleting
steroids. Potassium supplementation, diminution in dose, or
discontinuation of LASIX therapy may be required (see
WARNINGS AND PRECAUTIONS).
↓ furosemide
diuretic effect
Probenecid, which like furosemide, undergoes significant renal
tubular secretion, may also attenuate the effect of furosemide.
↑ radiocontrast
nephropathy
Patients who were at high risk for radiocontrast nephropathy
treated with furosemide experienced a higher incidence of
deterioration in renal function after receiving radiocontrast
compared to high-risk patients who received only intravenous
hydration prior to receiving radiocontrast.
CT
—
Caution should be exercised and the risks and benefits of the
combination or co-treatment with furosemide or with other
potent diuretics should be considered prior to the decision to
use. See PRECAUTIONS section, regarding increased mortality
in elderly patients with dementia concomitantly receiving
risperidone.
T
↑ salicylate
toxicity
Patients receiving high doses of salicylates in conjunction with
LASIX may experience salicylate toxicity at lower doses
because of competition for renal excretory sites.
T
↓ furosemide
absorption
Concurrent administration of LASIX and sucralfate should be
avoided, as sucralfate reduces the absorption of furosemide from
the intestine and hence weakens its effect.
T
Radiocontrast Agents
Radiocontrast
Agents
CT
Risperidone
Risperidone
Salicylates
Salicylates
Sucralfate
Sucralfate
Theophylline
↑ theophylline
The effects of theophylline may be increased.
effect
Legend: C= Case Study; CT= Clinical Trial; T= Theoretical
Theophylline
T
Interactions with other drugs have not been established.
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Drug-Food Interactions
Interactions with food have not been established.
Drug-Herb Interactions
Interactions with herbal product have not been established.
Drug-Laboratory Interactions
Interactions with laboratory tests have not been established.
DOSAGE AND ADMINISTRATION
Dosing Considerations
Careful observations for changes in blood pressure must be made when LASIX is used with
other antihypertensive drugs, especially during initial therapy. The dosage of other agents must
be reduced by at least 50% as soon as LASIX is added to the regimen to prevent excessive drop
in blood pressure. As the blood pressure falls under the potentiating effect of LASIX, a further
reduction in dosage or even discontinuation of other antihypertensive drugs may be necessary.
Recommended Dose and Dosage Adjustment
Adults (oral)
Edema
The usual initial dose of LASIX is 40 to 80 mg. Ordinarily a prompt diuresis ensues and the
starting dose can then be maintained or even reduced. If a satisfactory diuresis has not occurred
within 6 hours, succeeding doses should be increased by increments of 20 to 40 mg, if necessary.
Maximum daily dose: 200 mg. Once the effective single dose has been determined, it may be
repeated 1 to 3 times a day.
The mobilization of edema may be most efficiently and safely accomplished by utilizing an
intermittent dosage schedule in which LASIX is given for 2 to 4 consecutive days each week.
With doses exceeding 120 mg/day, careful clinical and laboratory observations are particularly
advisable.
Hypertension
A dosage schedule of 20 to 40 mg twice daily is recommended. Individualized therapy is of great
importance. It is further recommended, if 40 mg twice daily does not lead to a clinically
satisfactory response, to add other antihypertensive agents, rather than to increase the dose of
LASIX.
Lasix Oral Solution Product Monograph
Page 15 of 28
Pediatrics (oral)
LASIX therapy should be instituted in the hospital, in carefully selected patients, under close
observation with frequent monitoring of serum electrolytes.
Orally, the initial dose should be in the range of 0.5 to 1.0 mg/kg body weight.
The total daily dose (given in divided doses of 6 to 12 hours apart) should not exceed 2 mg/kg
orally. In the newborn and in pre mature babies, the daily dose should not exceed 1 mg/kg.
An intermittent dosage schedule should be adopted as soon as possible using the minimum
effective dose at the longest possible intervals. Particular caution with regard to potassium levels
is always desirable when LASIX is used in infants and children.
OVERDOSAGE
Symptoms
Dehydration, electrolyte depletion and hypotension may be caused by overdosage or accidental
ingestion. In cirrhotic patients, overdosage might precipitate hepatic coma.
The clinical picture in acute or chronic overdose depends primarily on the extent and
consequences of electrolyte and fluid loss, e.g. hypovolemia, dehydration, hemoconcentration,
cardiac arrhythmias (including A-V block and ventricular fibrillation). Symptoms of these
disturbances include severe hypotension (progressing to shock), acute renal failure, thrombosis,
delirious states, flaccid paralysis, apathy and confusion.
Treatment
The drug should be discontinued and appropriate corrective treatment applied: replacement of
excessive fluid and electrolyte losses; serum electrolytes, carbon dioxide level and blood
pressure should be determined frequently. Adequate drainage must be assured in patients with
urinary bladder outlet obstruction (such as prostatic hypertrophy).
No specific antidote to furosemide is known. If ingestion has only just taken place, attempts may
be made to limit further systemic absorption of the active ingredient by measures such as gastric
lavage or those designed to reduce absorption (e.g. activated charcoal).
For management of a suspected drug overdose, contact your regional Poison Control Centre.
Lasix Oral Solution Product Monograph
Page 16 of 28
ACTION AND CLINICAL PHARMACOLOGY
Mechanism of Action
Animal experiments using stop-flow and micropuncture techniques have demonstrated that
LASIX inhibits sodium reabsorption in the ascending limb of Henle's loop as well as in both
proximal and distal tubules. The action of LASIX on the distal tubule is independent of any
inhibitory effect on carbonic anhydrase or aldosterone.
LASIX may promote diuresis in cases which have previously proved resistant to other diuretics.
Pharmacodynamics
A continuous infusion of furosemide is more effective than repetitive bolus injections. Moreover,
above a certain bolus dose of the drug there is no significant increase in effect.
The effect of furosemide is reduced if there is lowered tubular secretion or intra-tubular albumin
binding of the drug.
Pharmacokinetics
Absorption
In man, LASIX is rapidly absorbed from the gastro-intestinal tract. The diuretic effect of
furosemide is apparent within one hour following oral administration and the peak effect occurs
in the first or second hour. The duration of action is 4-6 hours but may continue up to 8 hours.
Following intravenous administration of the drug, the diuresis occurs within 30 minutes and the
duration of action is about 2 hours.
Metabolism
A small fraction is metabolized by cleavage of the side chain.
Excretion
Urinary excretion is accomplished both by glomerular filtration and proximal tubular secretion,
together this accounts for roughly only 2/3 of the ingested dose, the remainder being excreted in
the feces.
The following table summarizes the elimination kinetics of furosemide.
Subjects
Normal
Normal
Renal insufficiency
Renal insufficiency
Table 1 - Summary of furosemide’s elimination kinetics.
Route of
Dose
Rate of
Biliary
Max. Serum
Administration
(mg)
Administration Excretion Concentration
Oral
40
—
10-15%
< 1µg /mL
I.V.
40
Bolus
10-15%
2.5 µg/mL
I.V.
1000
25 mg/min.
60%
53 µg /mL
I.V.
1000
Lasix Oral Solution Product Monograph
4 mg/min.
—
29 µg /mL
t½
(hr)
4.0
4.5
13.5
—
Page 17 of 28
Special Populations and Conditions
Pediatrics: Depending on the maturity of the kidney, the elimination of furosemide may be
slowed down. The metabolism of the drug is also reduced if the infant’s glucuronisation capacity
is impaired.
The terminal half-life is below 12 hours in infants with a post-conceptional age of more than
33 weeks.
In infants of 2 months and older, the terminal clearance is the same as in adults.
Geriatrics: The elimination of furosemide is slowed down due to reduced renal function in the
elderly.
Gender: Data unavailable.
Race: Data unavailable.
Hepatic Insufficiency: In liver failure, the half-life of furosemide is increased by 30% to 90%
mainly due to a larger volume of distribution. Additionally, in this patient group there is a wide
variation in all pharmacokinetic parameters.
Renal Insufficiency: In renal failure, the elimination furosemide is slowed down and the halflife prolonged; the terminal half-life may be up to 24 hours in patients with severe renal failure.
In nephrotic syndrome the reduced plasma protein concentration leads to a higher concentration
of unbound (free) furosemide. On the other hand, efficacy of furosemide is reduced in these
patients due to binding to intratubular albumin and lowered tubular secretion.
Furosemide is poorly dialyzable in patients undergoing hemodialysis, peritoneal dialysis and
CAPD.
Genetic Polymorphism: Data unavailable.
STORAGE AND STABILITY
Temperature
Oral solution: Store between 15° and 30°C. Protect from light.
Lasix Oral Solution Product Monograph
Page 18 of 28
DOSAGE FORMS, COMPOSITION AND PACKAGING
Lasix solution
Clear, slightly yellowish liquid, with an orange odour, containing 10 mg/mL furosemide.
Available in bottles of 120 mL.
Non-medicinal ingredients: alcohol, butylated hydroxyanisol, butylated hydroxytoluene,
glycerine, methylparaben, natural orange flavour, polysorbate 80, potassium sorbate, purified
water, sodium hydroxide and sorbitol.
Lasix Oral Solution Product Monograph
Page 19 of 28
PART II: SCIENTIFIC INFORMATION
PHARMACEUTICAL INFORMATION
Drug Substance
Proper name:
furosemide
Chemical name:
4-chloro-N-furfuryl-5-sulfamoyl-anthranilic acid
Molecular formula:
C12H11ClN2O5S
Molecular mass:
330.8
Structural formula:
Physicochemical properties: White to slightly yellow, crystalline powder. Practically
insoluble in water; freely soluble in acetone, in
dimethylformamide, and in solutions of alkali hydroxides;
soluble in methanol; sparingly soluble in alcohol; slightly
soluble in ether; very slightly soluble in chloroform,
melting at about 210°C (with decomposition).
CLINICAL TRIALS
No data available.
DETAILED PHARMACOLOGY
LASIX (furosemide) has no significant pharmacological effects other than on the renal function.
Renal Pharmacology
In dogs, furosemide demonstrated diuretic properties. Diuresis and sodium excretion were
induced by doses of 0.125 mg/kg administered intravenously or 0.5 mg administered orally.
Maximum water and sodium excretion is obtained by oral and intravenous doses of 12.5 and
25 mg/kg respectively. Increased potassium excretion can only be demonstrated with doses
exceeding 1 mg/kg. The onset of action is rapid after intravenous and oral administration and the
duration of activity is approximately 2 and 4 hours respectively.
Lasix Oral Solution Product Monograph
Page 20 of 28
Furosemide produces an immediate diuresis after intravenous administration and is effective
unilaterally after injection into a renal artery. Its action, therefore, is directly on the kidney. The
diuretic response is prompt and relatively brief. At the peak of diuretic response 30-40% of
filtered sodium load may be excreted, along with some potassium and with chloride as the major
anion. Furosemide augments the potassium output as a result of increased distal potassium
secretion. Its diuretic action is independent of changes in acid-base balance. Under conditions of
acidosis or alkalosis the diuretic produces chloruresis without augmentation of bicarbonate
excretion. It does not inhibit carbonic anhydrase.
On the basis of changes in free-water production furosemide inhibits sodium reabsorption in the
ascending limb of Helves loop. However, proximal sites of action are also involved, as
determined by micropuncture. Partial distal inhibition of sodium reabsorption is also possible. It
also decreases the urinary excretion of uric acid and prolonged administration may lead to
hyperuricemia. Since urate is transported in the proximal tubule, the effect of the drug on uric
acid excretion further suggests a proximal tubule site of action.
Administration of furosemide may induce extracellular metabolic alkalosis, primarily by virtue
of the disproportionate loss of chloride, but also, in part, as a result of the variable depletion of
potassium.
TOXICOLOGY
The acute toxicity of furosemide has been determined in four animal species:
Table 2 - ACUTE TOXICITY (LD50) OF FUROSEMIDE
(Approximate doses in mg/kg)
SPECIES
ORAL INTRAVENOUS
Mice
1000
300
Adult Rats
4600
700
Newborn Rats
400
-
Rabbits
700
400
Dogs
2000
over 400
The acute toxicity was characterized by signs of vasomotor collapse, sometimes accompanied by
slight convulsions. Surviving animals often became dehydrated and depleted of electrolytes. In
the newborn rats, intragastric injection of the drug caused hyperactivity and anorexia.
Lasix Oral Solution Product Monograph
Page 21 of 28
Chronic toxicity studies with furosemide were done in rats, dogs and monkeys.
1.
Rats: A one-year study was performed on one hundred albino rats at dosages of 0, 50,
100, 200 and 400 mg/kg/day orally. Seventy-six rats survived for one year. Ten rats from
the two highest dose groups died within the first 10 days of therapy. Histological
examination of those animals dying early revealed striking basophilic degeneration of the
myocardial fibres with infiltration and necrotic foci consistent with severe electrolyte
imbalance.
In the kidney, the most consistent pathological changes seen were degenerative changes
in the tubular epithelium manifested by swollen cells with increased density of the
cytoplasm. Occasionally, focal necrosis of the epithelium and decreased cell size were
evident, plus accumulation of some calcified material. These changes were considered
consistent with the nephropathy of potassium deficiency.
2.
Dogs: In a six-month study, eighteen out of twenty beagle dogs survived oral daily doses
of 0, 10, 30, 100 and 350 mg/kg. The most consistent pathological findings were renal
lesions consisting of calcifications and scarring of the renal parenchyma at all doses
above 10 mg/kg. The renal capsule above these lesions sometimes showed strikingly
enlarged lymph vessels with thickened walls.
3.
Rhesus Monkeys: In a 12-month study, daily oral doses of furosemide of 27 mg/kg and
60 mg/kg brought about pathological findings that consisted of dilated convoluted tubules
with casts in 3 out of 20 animals given 27 mg/kg and in 6 out of 9 animals given 60
mg/kg. These lesions were considered drug related.
Reproductive and teratological studies
Reproductive and teratological studies have been performed in mice, rats, rabbits, cats, dogs and
monkeys. With the exception of mice and rabbits, no abnormalities attributed to furosemide were
detected. Furosemide caused unexplained maternal deaths and abortions in the rabbit at a daily
dose of 50 mg/kg (approximately three times the maximum recommended human daily dose of
1000 mg orally) when administered between days 12 to 17 of gestation. In another study in
rabbits, a dose of 25 mg/kg caused maternal deaths and abortions. In a third study, none of the
pregnant rabbits survived a dose of 100 mg/kg. Data from the above studies indicate foetal
lethality which can precede maternal deaths.
The results of a mouse study and one of the three rabbit studies also showed an increased
incidence of distention of the renal pelvis and, in some cases, of the ureters in foetuses derived
from treated dams as compared to the incidence of foetuses from the control group.
Lasix Oral Solution Product Monograph
Page 22 of 28
REFERENCES
1.
CHAN, G.Y.F.: Competitive binding of bilirubin to albumin. M.Sc. Thesis, Department
of Experimental Medicine, McGill University, 1971.
2.
BRENNER, B.M., et al.: An inhibitory effect of furosemide on sodium reabsorption by
the proximal tubule of the rat nephron. J. Clin. Invest., 48: 290-300, 1969.
3.
FRASER, A.G., et al.: The effects of furosemide on the osmolality of the urine and the
composition of renal tissue. J. Pharmacol. Exp. Ther., 158: 475-486, 1967.
4.
SUKI, W., et al.: The site of action of furosemide and other sulfonamide diuretics in the
dog. J. Clin. Invest., 44: 1458-1469, 1965.
5.
MORRIN, P.A.F.: The effect of furosemide, a new diuretic agent, on renal concentrating
and diluting mechanisms. Can. J. Physiol. Pharmacol., 44: 129-137, 1966.
6.
STEIN, J.H., et al.: Differences in the acute effects of furosemide and ethacrynic acid in
man. J. Lab. Clin. Med., 17: 654-665, 1968.
7.
MUSCHAWECK, R. & HADJU, P.: Die salidiuretische Wirksamkeit der Chlor-N-(2furylmethyl)-5-sulfamyl-anthranilisaure. Arzn.-Forsch., 14: 44-47, 1964.
8.
BIRTCH, A.G., et al.: Redistribution of renal blood flow produced by furosemide and
ethacrynic acid. Circulation Res., 21: 869-878, 1967.
9.
HOOK, J.B., et al.: Effects of several saluretic diuretic agents on renal hemodynamics. J.
Pharmacol. Exp. Ther., 154: 667-673, 1966.
10.
QUICK, C.A. & HOPPE, W.: Permanent deafness associated with furosemide
administration. Ann. Otol., 34: 94-101, 1975.
11.
CUTLER, R.E., et al.: Pharmacokinetics of furosemide in normal subjects and
functionally anephric patients. Clin. Pharmacol. Ther., 15: 588-596, 1974.
12.
HUANG, C.M., et al.: Pharmacokinetics of furosemide in advanced renal failure. Clin.
Pharmacol. Ther., 16: 659-666, 1974.
13.
PRANDOTTA, J. & PRUITT, A.W.: Furosemide binding to human albumin and plasma
of nephrotic children. Clin. Pharmacol. Ther., 17: 159-166, 1975.
14.
KELLY, M.R., et al.: Pharmacokinetics of orally administered furosemide. Clin.
Pharmacol. Ther., 15: 178-186, 1974.
15.
RUPP, W.: The Pharmacokinetics of furosemide in health and renal disease. In "Die
Anwendung hoher Furosemiddosen in der Klinic", pp. 24-30, Medicus Verlag GmbH,
Berlin, 1973.
Lasix Oral Solution Product Monograph
Page 23 of 28
IMPORTANT: PLEASE READ
PART III: CONSUMER
INFORMATION
Pr
LASIX® ORAL SOLUTION
(furosemide solution Mfr. Std.)
This leaflet is part III of a three-part "Product
Monograph" published for LASIX® in Canada
and is designed specifically for Consumers. This
leaflet is a summary and will not tell you
everything about LASIX. Contact your doctor or
pharmacist if you have any questions about the
drug.
ABOUT THIS MEDICATION
What the medication is used for:
LASIX has been prescribed to you by your health
provider to treat your edema (water retention) or
hypertension (high blood pressure).
What it does:
LASIX belongs to a group of medicines known as
diuretic drugs which improve the elimination of
water and salts (electrolytes) in the urine.
When it should not be used:
Do not use LASIX if you are allergic to it or to any of
the components of its formulation (for list of
components see the section on “What the
nonmedicinal ingredients are”), or to any
sulfonamide-derived drugs. Ask your physician or
pharmacist if you are not sure what sulfonamidederived drugs are.
Do not use LASIX if:
• You are suffering kidney failure, hepatic (liver)
coma or precoma disease.
• You have electrolyte depletion (loss of blood
salts e.g. dehydration, hot weather, excessive
sweating…) or severe hyponatremia (low blood
sodium), hypokalemia (low blood potassium),
hypovolemia (low blood volume), hypotension
(low blood pressure) or dehydration until your
electrolytes and fluid balance are restored.
• Your newborn infant has jaundice (yellowing of
the skin and/or eyes) or infants suffering from
certain diseases (e.g. Rh incompatibility, familial
non-hemolytic jaundice (yellowing of the skin
and/or eyes without evidence of liver damage)).
Lasix Oral Solution Product Monograph
•
Do not breastfeed if you intend to use LASIX.
What the medicinal ingredient is:
Furosemide
What the nonmedicinal ingredients are:
10 mg/mL, oral solution: alcohol, butylated
hydroxyanisol, butylated hydroxytoluene, glycerine,
methylparaben, natural orange flavour, polysorbate
80, potassium sorbate, purified water, sodium
hydroxide and sorbitol
What dosage forms it comes in:
Oral solution of 10 mg/mL
WARNINGS AND PRECAUTIONS
LASIX IS A VERY STRONG WATER PILL
WHICH IF GIVEN IN EXCESSIVE AMOUNTS
CAN LEAD TO A PROFOUND WATER AND
ELECTROLYTE LOSS FROM THE BODY.
THEREFORE, CAREFUL MEDICAL
SUPERVISION IS REQUIRED. THE DOSE AND
DOSE SCHEDULE HAVE TO BE ADJUSTED TO
THE INDIVIDUAL PATIENT’S NEEDS.
BEFORE you use LASIX talk to your health provider
if:
• You have decreased blood pressure.
• You have liver disease or disorder.
• You have kidney disease or disorder.
• It is suspected you might be diabetic (high blood
sugar).
• You have decreased ability to pass urine.
• You had an organ transplant.
• You have gout.
• You have lupus or had an episode of lupus.
• You have been told by the doctor that you suffer
from a narrowing of the arteries that supply your
heart or brain.
• You have recently suffered from excess vomiting
or diarrhea.
• You intend to have a surgery and general
anesthesia (even at the dentist’s office), as there
may be a sudden fall in blood pressure associated
with general anesthesia.
• You are breastfeeding. LASIX is passed to the
infant during breastfeeding. Do not breastfeed if
you intend to take LASIX.
• You are pregnant, or think you might be
pregnant.
• You intend to change your eating habits.
Page 24 of 28
IMPORTANT: PLEASE READ
•
•
You are less than 18 years old.
You are older than 61 years old.
When administered to children, LASIX therapy
should be started in the hospital, in carefully selected
patients, under close observation with frequent blood
tests to measure electrolytes such as sodium,
potassium, chloride, magnesium and calcium.
For elderly patients, (over 61 years old), the dose
selection should be cautious, usually starting at the
low end of dosage range, reflecting the greater
frequency of decreased liver, kidney or heart
function.
Studies in elderly patients with dementia have shown
that taking LASIX with risperidone is associated with
a higher rate of death.
The administration of LASIX to diabetic patients
may result in possible decrease of diabetic control.
Dosage adjustments of the antidiabetic agent may be
needed.
There have been cases of ringing in the ears,
reversible and non-reversible deafness especially in
children. This is most true when the patient has
severe kidney disease or is taking drugs that are
known to sometimes damage the ears while they are
taking LASIX. Your doctor will decide if LASIX is
the right medication for you/your child based on your
particular condition.
LASIX should not be used in pregnant women or in
women of childbearing potential unless in the opinion
of the attending physician the benefits to the patient
outweigh the possible risk to the foetus. Treatment
during pregnancy requires monitoring of fetal growth
by your doctor.
If you are suffering from hyperuricemia (high uric
acid levels in your blood), taking LASIX can
sometimes make a gout attack more likely.
Almost all patients can drive or operate machinery
while taking LASIX, but you should not perform
these tasks, which may require attention, until you
know how you tolerate your medicine.
Lasix Oral Solution Product Monograph
INTERACTIONS WITH THIS MEDICATION
Before using LASIX, tell your health provider about
medication you are currently taking. This way
appropriate adjustment and decision can be taken for
your treatment with LASIX.
Below are drugs or drug classes that may interact
with LASIX. These include:
• Drugs to reduce blood pressure (eg. ACE
inhibitors, angiotensin II receptor antagonist).
• Diuretics (waterpills), including ethacrynic acid
• Pressor amines such as epinephrine (a medication
used to treat life-threatening allergic reactions).
• Medication to treat diabetes, including insulin.
The administration of LASIX to diabetic patients
may result in possible decrease of diabetic control.
Dosage adjustments of the antidiabetic agent may
be needed.
• Theophylline, a medication used to treat asthma,
chronic bronchitis, and other lung diseases.
• Cisplatin (anti-cancer drug)
• Probenecid (medicine used to treat gout).
• Antibiotics (e.g cephalosporins, aminoglycosides)
• Certain pain and anti-inflammatory drugs (e.g
non-steroidal anti-inflammatory drugs [NSAIDs],
acetyl-salicylic acid, indomethacin)
• Drugs used in the treatment of rheumatoid arthritis
(methotrexate, cyclosporin).
• Drugs used to treat epilepsy (e.g. phenytoin,
carbamazepine, phenobarbital).
• Risperdal, a drug used to treat dementia.
• Lithium (medicine used to treat bipolar
depression).
• Sucralfate (antacid drug)
• Sedatives such as phenobarbital or chloral hydrate
• Stimulant laxatives and drugs which may induce
low potassium levels (hypokalemia) such as
glucocorticoids, and medicine derived from
licorice (eg. carbenoxolone).
• Drugs known to be harmful to the ear (ototoxic) as
for instance aminoglycosides antibiotics,
ethacrynic acid (a “water pill”) and cisplatin (a
drug used to treat some types of cancer).
• Drugs known to be harmful to the kidney.
• Substances used during certain radiological
investigations (radiocontrast agents).
• Digitalis (digoxin)
• Certain steroids
• Levothyroxine, a drug used to adjust your thyroid
hormone levels
Page 25 of 28
IMPORTANT: PLEASE READ
PROPER USE OF THIS MEDICATION
During long-term therapy a high-potassium diet may
be recommended. You should not be on a strict salt
restricted diet. Potassium supplements may be
required. Your doctor will monitor your blood tests
for blood sugar, potassium and other electrolytes and
to monitor liver and kidney function. This is
especially important if you have other medical
conditions such as diabetes, take other medications or
the patient is an infant or child.
Usual dose:
Adults (oral) for edema and high blood pressure:
Orally, the initial dose should be in the range of
0.5 to 1.0 mg/kg body weight.
The total daily dose (given in divided doses of 6 to 12
hours apart) should not exceed 2 mg/kg orally. In the
newborn and in premature babies, the daily dose
should not exceed 1 mg/kg.
Overdose:
In case of drug overdose, contact a heath care
practitioner, hospital emergency department or
regional Poison Control Centre immediately, even if
there are no symptoms.
SIDE EFFECTS AND WHAT TO DO ABOUT THEM
It is important that you take LASIX as prescribed by
your doctor.
Along with its beneficial effects, LASIX like all other
drugs may sometimes cause undesirable effects.
Usually your doctor will prescribe LASIX at a dose
of 20 to 80 mg per day, which you could take as
single or 2-3 divided doses, based on the type of
administration your physician considers to be the
most appropriate for your condition.
These may include: blurring of vision, constipation,
diarrhea, dizziness, dry mouth, fatigue, tachycardia,
arrhythmia (heart rhythm disturbance), feeling of
pressure in the head, increase in the amount and
frequency of your urine, leg cramps, mental
confusion, nausea, sweating, thirst, vomiting, hepatic
encephalopathy (altered mental state due to liver
disease). Talk to your doctor or pharmacist if you
experience any of the above.
Maximum daily dose: 200 mg.
When prescribed to children, LASIX is usually
administered in the form of a solution and at a dose
that will be determined by the health care provider.
The oral solution should be taken on an empty
stomach.
You should always respect the prescribed interval
between the doses. Never change the dose of LASIX
you are taking unless your doctor tells you to.
Stop taking LASIX and contact your doctor
immediately if you experience an allergic reaction or
any severe side effect.
SERIOUS SIDE EFFECTS, HOW OFTEN THEY
HAPPEN AND WHAT TO DO ABOUT THEM
Symptom / effect
This drug is specifically prescribed for you or a child
in your care. Do not give it to others, even if they
have the same symptoms, and you yourself must not
use it for any condition than the one for which it was
prescribed.
Pediatrics (oral):
LASIX therapy should be instituted in the hospital, in
carefully selected patients, under close observation
with frequent monitoring of blood tests including
electrolytes. The doctor will decide what the best
dose for each child.
Lasix Oral Solution Product Monograph
Talk with your
doctor or
pharmacist
immediately
Only
if
severe
Hearing problems;
deafness, sometimes
non-reversible
Fever, sore throat,
fatigue, lesions in the
mouth or on the lips
Skin rash and/or
blistering
In all
cases
Stop taking
drug and seek
immediate
emergency
medical
attention



Page 26 of 28
IMPORTANT: PLEASE READ
SERIOUS SIDE EFFECTS, HOW OFTEN THEY
HAPPEN AND WHAT TO DO ABOUT THEM
Symptom / effect
Talk with your
doctor or
pharmacist
immediately
Only
if
severe
In all
cases

Hives and/or itching
Abdominal pain


Difficulty to urinate
Low blood pressure
(hypotension):
dizziness when rising
to a standing position,
impaired concentration
and lightheadedness
Yellow coloration of
the skin (jaundice)
Dehydration and/or
abnormal blood tests:
dryness of the mouth,
thirst, weakness,
dizziness, fainting or
loss of consciousness,
lethargy, drowsiness,
restlessness, muscle
pain or cramps,
muscular fatigue,
hypotension, racing or
irregular heartbeats,
nausea and vomiting,
sweating, increases in
blood sugar levels,
increased urination,
mental confusion,
headache
Muscle problems:
unexplained muscle
pain, tenderness,
weakness, cramps
Pseudo- Bartter
syndrome: abnormal
blood tests, fatigue,
muscle weakness,
diarrhea, dehydration,
increased thirst,
increased urination,
low blood pressure,
irregular heartbeats
Blurred vision
Stop taking
drug and seek
immediate
emergency
medical
attention



SERIOUS SIDE EFFECTS, HOW OFTEN THEY
HAPPEN AND WHAT TO DO ABOUT THEM
Symptom / effect
Talk with your
doctor or
pharmacist
immediately
Only
if
severe
Allergic reactions:
eyes sensitive to light,
tingling of fingers or
toes, fever
Blood clots: pain,
swelling tenderness in
your leg or arm, warm,
red skin and a heavy
feeling in the affected
area
Failure of the kidneys:
weakness, trouble
breathing, swelling,
fast or irregular
heartbeat, confusion,
decrease or inability to
urinate, loss of
appetite, coma and
death
In premature babies:
discoloured urine
and/or blood in the
urine/diaper, fever and
chills, vomiting,
excessive crying or
other signs the baby is
in pain
In premature babies:
poor weight gain
In all
cases
Stop taking
drug and seek
immediate
emergency
medical
attention





Although not all of the above side effects are
common, if you experience one of these while you
are in the hospital or at home, talk to your doctor or
pharmacist immediately.


This is not a complete list of side effects. For any
unexpected effects while taking LASIX, contact your
doctor or pharmacist.
HOW TO STORE IT

Lasix Oral Solution Product Monograph
Store your solution at room temperature (15° –
30°C). Protect from light.
Page 27 of 28
IMPORTANT: PLEASE READ
There is an expiration date on the label. Do not use
the medicine after this date.
Return any leftover solution to the pharmacist, unless
the doctor tells you to keep them at home.
As with all medicines, keep LASIX out of reach of
children.
REPORTING SUSPECTED SIDE EFFECTS
You can report any suspected adverse reactions
associated with the use of health products to the
Canada Vigilance Program by one of the following 3
ways:
• Report online at:
www.healthcanada.gc.ca/medeffect
• Call toll-free at 1-866-234-2345
• Complete a Canada Vigilance Reporting Form
and:
- Fax toll-free to 1-866-678-6789, or
- Mail to: Canada Vigilance Program
Health Canada
Postal Locator 0701E
Ottawa, ON K1A 0K9
Postage paid labels, Canada Vigilance Reporting
Form and the adverse reaction reporting guidelines
are available on the MedEffect™ Canada Web site at
www.healthcanada.gc.ca/medeffect.
NOTE: Should you require information related to the
management of side effects, contact your health
professional. The Canada Vigilance Program does
not provide medical advice.
MORE INFORMATION
This document plus the full product monograph,
prepared for health professionals can be found at
www.sanofi.ca or by contacting the sponsor, sanofiaventis Canada Inc. at: 1-800-265-7927.
This leaflet was prepared by sanofi-aventis Canada
Inc.
Last revised: September 20, 2016
Lasix Oral Solution Product Monograph
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